The research career award (RCA/K02) plan outlined in this proposal will serve as a logical extension and critical support of my research career development in Women's Health/Drug Abuse at the University of Kentucky. Specifically, I propose to obtain additional training in order to extend my NIDA-funded research concerning intravenous drug abuse (IDU) in females to include HIV in the model. Such a cross-disciplinary effort is essential, as IDU is a major risk factor for HIV infection. Women IDU represent the fastest growing population of HIV positive individuals in the US. Currently, there is a paucity of neuroscientists with training in neurovirology and drug abuse models. Release time from teaching duties generated by this RCA will allow me the opportunity for a period of intensive research focus on IDU and HIV neurobiology. This training will strengthen my research efforts in this fast growing area by allowing me to work with infectious HIV+ cells and tissues. The specific research program proposed in this application is part of two NIDA funded R01 projects which together pose the major question: Are biological gender differences in responsiveness to (repeated) cocaine predisposing females to HIV-induced neurotoxicity? The hypothesis is: Estrogens will act as protective agents for the combined effects of repeated IV cocaine administration and gp120/Tat neurotoxicity. In this project, first, we will determine whether steroid hormones are neuroprotective against the combined effects of gp120/Tat and cocaine in cultured human fetal neurons. Second, I plan to extend our rodent model into work with human HIV+ brain tissue. These proposed studies will contribute to the scientific development of the applicant in the area of women's health and drug abuse and further our knowledge with regard to HIV neurotoxicity in this population. This training is essential to my research career progression (as rats do not develop AIDS) and this RCA will allow me the release time to critically test my research hypothesis in AIDS brain tissue from male and female drug abusers.